Aloe-emodin suppresses prostate cancer by targeting the mTOR complex 2

Kangdong Liu, Chanmi Park, Shengqing Li, Ki Won Lee, Haidan Liu, Long He, Nak Kyun Soung, Jong Seog Ahn, Ann M. Bode, Ziming Dong, Bo Yeon Kim, Zigang Dong

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.

Original languageEnglish (US)
Pages (from-to)1406-1411
Number of pages6
JournalCarcinogenesis
Volume33
Issue number7
DOIs
StatePublished - Jul 2012

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010-0029233). or Leap Research Program (No. 2010-0029233). -WCI: World Class Institute Program founded by the Korea Research Foundation, Ministry of Education, Science and Technology. or WCI 2009-002.

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